Core B is a central component of the Emory Udall Center of Excellence for Parkinson's disease research. The Core will provide neuroanatomical and behavioral expertise that will be essential to the successful completion of all projects proposed in this application. In contrast to traditional service cores, core B will not only provide technical expertise to the projects, but will play an active role in the study design as well as collection, analysis and interpretation of data related to each project. The proposed work that will be achieved by the core for the different projects include : (1) Project 1: In this project, the core will be responsible for immuno-electron microscopic studies of the localization of muscarinic receptor subtypes in the ventral motor thalamic nuclei of normal mice, and mouse models of Parkinson's disease. These findings will complement the physiological data Dr. Jaeger and his colleagues will collect on the role of these receptors in the regulation of firing activity in the parkinsonian thalamus. (2) Project 2: In this project, light and electron microscopy immunostaining methods will be used to characterize plastic changes in the synaptic connectivity and GABA receptor expression in the ventral motor thalamic nuclei of parkinsonian monkeys with lesions of the internal globus pallidus. These findings will be essential for the interpretation of the electrophysiological and behavioral effects of pallidotomies on thalamic activity and parkinsonian behavior. (3) Project 3: The core will determine the effects of TrkB agonists on striatal spine loss in mouse and monkey models of Parkinson's disease and assess the antiparkinsonian efficacy of TrkB agonist in parkinsonian monkeys. Together, findings of these studies will contribute to the characterization of a novel restorative therapy that could be used in patients with Parkinson's disease. (4) Project 4: In this project. Core B will provide a detailed quantitative assessment of the cellular and ultrastructural localization of the Ml and M4 muscarinic receptor immunoreactivity in the subthalamic nucleus and the substantia nigra pars reticulata. Such information will be critical for the interpretation of electrophysiological and behavioral effects induced by the different muscarinic receptor antagonists used in this project.